1、Biodegradable Polymers: Chemistry, Degradation and Applications,Definition,A “biodegradable” product has the ability to break down, safely, reliably, and relatively quickly, by biological means, into raw materials of nature and disappear into nature.Natures way: every resource made by nature returns
2、 to nature. Nature has perfected the system we just need to figure out how,How long does it take?,Cotton rags 1-5 months Paper 2-5 months Rope 3-14 months Orange peels 6 months Wool socks 1 to 5 years Cigarette butts 1 to 12 years Plastic coated paper milk cartons 5 years Plastic bags 10 to 20 years
3、 Nylon fabric 30 to 40 years Aluminum cans 80 to 100 years Plastic 6-pack holder rings 450 years Glass bottles 1 million years Plastic bottles May be never,What is Polymer Degradation?,polymers were synthesized from glycolic acid in 1920s At that time, polymer degradation was viewed negatively as a
4、process where properties and performance deteriorated with time.,Why Would a Medical Practitioner Like a Material to Degrade in the Body?,Do not require a second surgery for removal Avoid stress shielding Offer tremendous potential as the basis for controlled drug delivery,Medical Applications of Bi
5、odegradable Polymers,Wound management Sutures Staples Clips Adhesives Surgical meshes Orthopedic devices Pins Rods Screws Tacks Ligaments,Dental applications Guided tissue regeneration Membrane Void filler following tooth extraction Cardiovascular applications Stents Intestinal applications Anastomo
6、sis rings Drug delivery system Tissue engineering,Biodegradable Polymers,Carbonyl bond to,O N S,Where X= O, N, S,Ester,Amide,A.,Thioester,Where X and X= O, N, S,B.,Carbonate,Urethane,Urea,C.,Imide,Anhydride,Where X and X= O, N, S,Biodegradable Polymers,Biodegradable Polymers,Acetal: Hemiacetal: Ethe
7、r Nitrile Phosphonate Polycyanocrylate,Biodegradable Polymers Used for Medical Applications,Natural polymers Fibrin Collagen Chitosan Gelatin Hyaluronan . Synthetic polymers PLA, PGA, PLGA, PCL, Polyorthoesters Poly(dioxanone) Poly(anhydrides) Poly(trimethylene carbonate) Polyphosphazenes .,Syntheti
8、c or Natural Biodegradable Polymers? Why We Prefer Synthetic Materials:,Tailor-able properties Predictable lot-to-lot uniformity Free from concerns of immunogenicity Reliable source of raw materials,Degradation Mechanisms,Enzymatic degradation Hydrolysis (depend on main chain structure: anhydride es
9、ter carbonate)Homogenous degradation Heterogenous degradation,Degradation can be divided into 4 steps:,water sorption reduction of mechanical properties (modulus & strength) reduction of molar mass weight loss,Polymer Degradation by Erosion (1),Degradation Schemes,Surface erosion (poly(ortho)esters
10、and polyanhydrides) Sample is eroded from the surface Mass loss is faster than the ingress of water into the bulkBulk degradation (PLA,PGA,PLGA, PCL) Degradation takes place throughout the whole of the sample Ingress of water is faster than the rate of degradation,Erodible Matrices or Micro/Nanosphe
11、res,(a) Bulk-eroding system(b) Surface-eroding system,General Fabrication Techniques,Molding (formation of drug matrix)compression moldingmelt moldingsolvent casting,Molding ( compression molding ) (1),Polymer and drug particles are milled to a particle size range of 90 to 150 mDrug / Polymer mix is
12、 compressed at 30,000 psiFormation of some types of tablet / matrix,Molding ( melt molding / casting ) (1),Polymer is heated to 10C above it melting point ( Tm ) to form a viscous liquidMix drug into the polymer meltShaped by injection molding,Molding ( melt molding / casting ) (2),Advantages More u
13、niform distribution of drug in polymer Wide range of shapes possibleDisadvantages Thermal instability of drugs (heat inactivation) Drug / polymer interaction at high temperature Cost,Molding ( Solvent casting ) (1),Co-dissolve drug and polymer in an organic solvent Pour the drug / polymer solution i
14、nto a mold chilled under dry iceAllow solvent to evaporateFormation of a drug-polymer matrix,Molding ( Solvent casting ) (2),Advantages Simplicity Room temperature operation Suitable for heat sensitive drugsDisadvantages Possible non-uniform drug distribution Proper solvents for drugs and polymers F
15、ragility of the system Unwanted matrix porosity Use of organic solvents / Solvent residues,Polyesters,Comparison,Mobley, D. P. Plastics from Microbes. 1994,Factors Influence the Degradation Behavior,Chemical Structure and Chemical Composition Distribution of Repeat Units in Multimers Molecular Weigh
16、t Polydispersity Presence of Low Mw Compounds (monomer, oligomers, solvents, plasticizers, etc) Presence of Ionic Groups Presence of Chain Defects Presence of Unexpected Units Configurational Structure Morphology (crystallinity, presence of microstructure, orientation and residue stress) Processing
17、methods & Conditions Method of Sterilization Annealing Storage History Site of Implantation Absorbed Compounds Physiochemical Factors (shape, size) Mechanism of Hydrolysis (enzymes vs water),Poly(lactide-co-glycolide) (PLGA),(JBMR, 11:711, 1977),Factors That Accelerate Polymer Degradation,More hydro
18、philic backbone. More hydrophilic endgroups. More reactive hydrolytic groups in the backbone. Less crystallinity. More porosity. Smaller device size.,Methods of Studying Polymer Degradation,Morphological changes (swelling, deformation, bubbling, disappearance) Weight lose Thermal behavior changes Differential Scanning Calorimetry (DSC) Molecular weight changes Dilute solution viscosity Size exclusion chromatograpgy(SEC) Gel permeation chromatography(GPC) MALDI mass spectroscopy Change in chemistry Infared spectroscopy (IR) Nuclear Magnetic Resonance Spectroscopy (NMR) TOF-SIMS,
